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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Tuesday, May 2, 2023
According to Syreeta L. Tilghman, PhD, of Florida A&M University, Tallahassee, and colleagues, breast cancer cells seem to respond favorably to the growth inhibitory and antimigratory properties of the novel phytochemical glyceollin plus the dual EGFR and HER2 inhibitor lapatinib, with letrozole-resistant cells exhibiting increased sensitivity to cell-cycle progression. These findings, which were presented during the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 406/1), may inform the second-line therapy landscape for aromatase inhibitor–resistant cancers.
“As breast cancer cells transition from letrozole-sensitive to letrozole-resistant, they overexpress EGFR, MAPK, and HER2 and acquire enhanced motility and epithelial-mesenchymal transition–like characteristics that are attenuated and reversed by glyceollin treatment, respectively,” the investigators commented. “We hypothesized that combination therapy could reverse motility in hormone-independent, letrozole-resistant cells compared with aromatase inhibitor–sensitive cells by altering proteins involved in motility and cell-cycle progression.”
In this study, both aromatase inhibitor–sensitive and letrozole-resistant breast cancer cells were exposed to 10 μM of glyceollin with or without 5 μM of lapatinib. A time-dependent decrease in cell viability was observed in both cell lines with and without the addition of lapatinib. Compared with glyceollin alone, combination therapy seemed to prevent migration in a higher percentage of both aromatase inhibitor–sensitive (88% vs. 55%) and letrozole-resistant (93% vs. 51%) cells.
According to the researchers, the treatment choice did not seem to impact the aromatase inhibitor–sensitive cell-cycle distribution; however, combination therapy was found to reduce the number of letrozole-resistant cells in the G1/G0 phase while simultaneously causing an accumulation of cells in both the S and G2/M phases. Although treatment with glyceollin plus lapatinib did not appear to influence protein expression in aromatase inhibitor–sensitive cells, the expression of cyclin B1 was selectively decreased in their letrozole-resistant counterparts.
Disclosure: The study authors reported no conflicts of interest.
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